1. Field of the Invention
The present invention relates to a pesticide having an insecticide, acaricide and nematicide action which at least includes an isoquinoline alkaloid and at least a flavonoid, same produce important synergic interactions in their biological activity, said invention is efficient to control plagues and its main characteristics are: high specificity on target plagues, low toxicity for mammals, low persistence in the environment and in which the active ingredients could come, although not exclusively, from plant extracts.
Likewise, the present invention relates to a manufacturing process, consisting of two stages, where the first stage refers to obtaining and standardizing the active principles of the pesticide: isoquinoline alkaloids and flavonoids, as well as a second stage related to its commercial formula.
2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 37 CFR 1.98.
Historically, the first generation of botanical pesticides dates back to the XIX Century, when some compounds of a botanical origin such as alkaloids, rotenone and rotenoid compounds, pyrethrins and essential oils were identified.
Alkaloids are nitrogenous secondary metabolites, generally of a basic character and most of these compounds are biosynthetized from amino acids. Nicotine is an alkaloid isolated from the tobacco plant, mainly form Nicotiana tabacum and Nicotiana rustica (Solanaceae), and it is considered as a toxic and dangerous pesticide for humans. It is a neurotoxin that specifically acts on the nicotinic cholinergic receptors by delaying the closing of the sodium channels, this causes paralysis before death.
Sabadilla is a pesticide obtained from the Schoenocaulon officinale seeds. Its active principles are mainly the cevadine, veratridine alkaloids, which are esters of a steroidal alkaloid called veracevine which are toxic for mammals (DL50 13 mg/kg), but in commercial preparations that include it as an active ingredient its concentration is less than 1%. The mechanism action of this type of alkaloids is similar to that of pyrethrins.
Ryania is a powder obtained from the Ryania speciosa Wood and its activity is attributed to the ryanodine (<1%), a pyrrole-2-carboxylic ester of a complex diterpene (ryanodol). Ryanodine acts as a pesticide interfering with calcium release in the muscular tissue causing a sharp muscular contraction which can be followed by paralysis.
Rotenone is an isoflavonoid and the main pesticide component of the roots or rhizomes of the tropical leguminous Derris, Lonchocarpus and Tephrosia. Most of the rotenone used at present comes from Lonchocarpus, also known as cube root. About 44% of rotenone and 22% of deguelin, another rotenoid is extracted from this root. Rotenone is a mitochondrial poison which blocks electron transportation and prevents the production of energy. Rotenone is toxic for humans (DL50 132 mg/kg) and although commercial formulations use less toxic levels than those of lethal doses, this pesticide has a limited use in agriculture.
Pyrethrum is extracted from the chrysanthemum flowers (Tanacetum cinerarifolium, Asteraceae) and it is a mixture of 6 secondary metabolites: pyrethrins I and II, cinerin I and II and jasmolins I and II. Pyrethrum is a neurotoxin that causes immediate paralysis in insects because it blocks voltage sodium channels that depend on axons. This action mechanism is similar to that of the organochlorate pesticide DDT, but as opposed to this, pyrethrins show moderate toxicity for mammals. In spite of its immediate action, most of the insects recover, unless pyrethrum is formulated with a synergic agent. Pyrethrum constitutes approximately 80% of the total of commercial botanical pesticides in the world.
Essential oils are the main volatile aromatic principles of plants, of a complex chemical nature that mainly include terpenoids, where monoterpenes are the biggest group and the sesquiterpenes appear in a smaller proportion (these contain 10 and 15 carbon atoms, respectively) and more rarely diterpenes (20 carbon atoms). Essential oils, mainly monoterpenes are specifically toxic against pest insects due to their neurotoxic mechanism which acts on the octopaminergic receptors in the system which transmits nervous impulses in invertebrates. Essential oils due to their volatile nature probably enter the insect through the respiratory system and at present are mainly used to protect domestic animals and clothes (against moths), and also as wood preservatives.
Phytosanitary products of a plant origin in this first generation were substituted by pesticides product of chemical synthesis as organochlorate compounds, organophosphorus and carbamates, which caused severe environmental contamination problems and resistance in insects, in addition to harmful effects in non-target organisms. As an answer to all of these problems a strictly chemical strategy arose where the modification of the structure of natural products was sought for to obtain compounds that would have better pesticide activity and less toxicity for mammals, these search originated pyrethroids. The interest to develop products of a plant origin was also importantly renewed, and chemical ecology emerged where chemists, biochemists, toxicologists and specialists in plant protection joined efforts in the research of natural products of a botanical origin to control pest with a minimum of environmental problems. This established the rules for the second generation of botanical pesticides.
The more detailed study of the relationship between plants and insects, allowed researches to know that evolution has given plants chemical mediators implied in the communication between species, same that are known as semiochemical compounds which are regarded as non-nutritious compounds produced by an organism that affect behavior or the biology of individuals of the same species (pheromones) or of different species (allelochemical molecules). The latter have a series of effects before harmful insects and are classified according to their mode of action as defensive, toxic, repellent or discouraging, antiphagostimulant or digestive inhibitors, and attracting substances, among others, and depending on their chemical composition and intensity they reveal information in respect to the physiological status of the plant and the stress in which it is and modify behavior or the biology of an organism of another species. These molecules generally act at a low dose and have a specific action and their toxicity for mammals is low.
This second generation of botanical pesticides allowed western researches to rediscover neem used in India since ancestral times. From the neem tree seeds (Azadirachta indica, Meliaceae) two kinds of pesticides can be obtained: Neem oil (essential oil) and azadirachtin (10-25%), a limonoid of the meliacine type. Limonoids have mainly been isolated from the Meliaceae (meliacines) and Rutacea (limonoids of citric plants) families. Limonoides are modified triterpenes or tetranortriterpenoids, highly oxygenated derived from the 4,4,8-trimethyl-17-furanosylsteroid precursor. Limonoids of the meliacine type are structurally more complex than limonoids from citrus plants and have a higher oxidation level. Azadirachtin carries out its pesticide action by blocking synthesis and hormone release during ecdysis of mature insects which as a consequence inhibits their growth and development, and in adult insects, through a similar mechanism, causes sterility. Azadirachtin is also a powerful antifeedant.
In the last few years greater acceptance in the world market of new alternatives for the integral management of plants has been observed, due to the resistance developed by insects and to other undesirable side effects originated by the indiscriminate use of conventional synthetic pesticides. But, on the other hand there are also several factors that limit the use of botanical pesticides because of inconsistent practical results probably caused by the lack of chemical standardization of the formulations; the non-competitive price compared to that of classic pesticides; and inappropriate formulations and application against a limited range of pest.
In previous works on botanical pesticide related to the present invention, patent US2005/0244445 was found, same makes reference to the synergic effect on insecticide activity of formulations based on essential oils, insecticide soaps and/or pyrethrins, with detergents such as sodium lauryl sulfate (SLS), sodium docedyl sulfate (SDS) or lecithin.
On the other hand, in American patents U.S. Pat. No. 6,372,239 and US2008/0300225 the use of tetracycle quinolizidinic alkaloids: matrine and oxymatrine, isolated in the roots of Sophora, individually or present in a mixture of alkaloids to carry out a synergetic effect on pest control is described. The pesticide activity of these alkaloids is attributed to its inhibition effect on the acetylcholinesterase enzyme, thus inhibiting degradation of the acetylcholine neurotransmitter. When the concentration of acetylcholine is increased, hyperexcitability of the Central Nervous System is caused; this originates the death of insects.
In addition, Stermitz et. al. (2002), reported the synergetic effect of two flavones: chrisosplenetine and chrysosplenol D (isolated from Artemisia annua L. extract) in the antimicrobial activity shown by berberine against Staphylococcus aureus. It was determined that these flavonoids block berberine extrusion from the bacterial cell by inhibiting the multidrug efflux (MDF) pump, thus allowing them to carry out their bactericide action.
Lastly, Chinese patent CN 2004-10022134 describes the process to manufacture a pesticide to prevent diseases in plants caused by pathogenic micro-organisms and to promote plant growth, which has as active ingredients a mixture of 0.06%-0.26% of berberine hydrochloride; 0.01-0.06% of matrine and 0.23-1.38% of flavonoids.
In this sense, the present invention refers to obtaining and manufacturing a pesticide having an insecticide, acaricide and nematicide action, new and efficient for integrated pest management which attack plants, fruits and/or animals, based on a new mixture of isoquinoline alkaloids and flavonoids from, although not exclusively, plant extracts that show important synergic interactions in their pesticide activity.
The isoquinoline alkaloids of the present invention may come from, although not exclusively, the Papaveraceae family and the flavonoids from the Asteraceae family. Both types of secondary metabolites can also be chemically synthesized.
In the Papaveracea family, the presence of isoquinoline alkaloids is known; said derive from protoberberine, tetrahydroberberine, protopine and benzophenanthridine, and spirobenzylisoquinoline and cularine in Fumarioideae, as well as from other groups that give them their known pharmacological properties: derived from aporphine, morphinane, pavine, isopavine, narceine and rhoeadine. At least other 20 alkaloids in plants belonging to this family are know; these are: cheilanthifoline, chelerytrine, N-norchelerytrine, dihydrochelerytrine, coptisine, cryptopine dihydrosanguinarine, norsanguinarine, scoulerine, stylopine, muramine, thalifoline, reframidine and oxyhydrastinine. These secondary metabolites are responsible for the medicinal properties attributed to the family.
In the Asteraceae family, especially of the genus Cirsium, a series of compounds having a pesticide activity of a different chemical nature have been isolated; these include flavonoids, sterols, triterpenes, alkaloids, polyacetylenes, acetylenes, sesquiterpenes, lactones, phenolic acids and lignans. Within the flavonoids isolated from Cirsium, glycosylated derivatives of apigenin, cirsimaritin, campherol, linarin, luteolin, pectolinarin y quercetin are included.